Novel therapeutic strategies for stimulating regeneration of human heart muscle would significantly improve clinical outcomes for patients experiencing a heart attack. In contrast to humans, adult zebrafish naturally regenerate their heart muscle following injury. Our lab recently discovered that the Notch signaling pathway becomes activated following cardiac injury in zebrafish and is required for stimulating growth of new cardiac muscle. The goal of this application is to gain new mechanistic insight into how Notch stimulates heart regeneration in fish with the long-term goal of informing new therapeutic strategies for redirecting or repurposing activated Notch for clinical benefit in humans.